Contribution of the interferon-gamma release assay to tuberculosis diagnosis in children and adolescents.

SETTING: As conclusive data on the performance of interferon-gamma release assays (IGRAs) in paediatric TB are lacking, many guidelines do not recommend their use for TB diagnosis in this population in Brazil. OBJECTIVE: To evaluate the performance of an IGRA by investigating its concordance with the tuberculin skin test (TST) and the role of IGRAs in clinical management and treatment outcomes in children with TB. DESIGN: A historic cohort study was used to evaluate the performance of T-SPOT®.TB (ELISpot) and other tests, such as the TST, in paediatric patients with or without immunodeficiency who were under investigation for latent tuberculous infection (LTBI) or active tuberculosis (TB). RESULTS: Of 86 paediatric patients evaluated, 41 (48%) were immunocompetent and 45 (52%) immunocompromised. All patients underwent T-SPOT.TB, while 63 underwent both ELISpot and TST; test results were concordant in 50 patients (79.4%): 22/31 (71%) in immunocompetent (κ = 0.418, P = 0.02) and 28/32 (87.5%) in immunocompromised patients (κ = 0.526, P = 0.003). TB was diagnosed on the basis of the ELISpot result in 21% (18/86) cases; the contribution of the ELISpot assay was greater in immunocompetent patients than in those who were immunocompromised (13/41, 31.7% vs. 5/45, 11.1%, χ2 P = 0.038). CONCLUSION: ELISpot and TST results were moderately concordant in both groups of patients. ELISpot contribution was higher among immunocompetent patients than among immunocompromised patients.

Improvement in the outcome of invasive fusariosis in the last decade.

Invasive fusariosis (IF) has been associated with a poor prognosis. Although recent series have reported improved outcomes, the definition of optimal treatments remains controversial. The objective of this study was to evaluate changes in the outcome of IF. We retrospectively analysed 233 cases of IF from 11 countries, comparing demographics, clinical findings, treatment and outcome in two periods: 1985-2000 (period 1) and 2001-2011 (period 2). Most patients (92%) had haematological disease. Primary treatment with deoxycholate amphotericin B was more frequent in period 1 (63% vs. 30%, p <0.001), whereas voriconazole (32% vs. 2%, p <0.001) and combination therapies (18% vs. 1%, p <0.001) were more frequent in period 2. The 90-day probabilities of survival in periods 1 and 2 were 22% and 43%, respectively (p <0.001). In period 2, the 90-day probabilities of survival were 60% with voriconazole, 53% with a lipid formulation of amphotericin B, and 28% with deoxycholate amphotericin B (p 0.04). Variables associated with poor prognosis (death 90 days after the diagnosis of fusariosis) by multivariable analysis were: receipt of corticosteroids (hazard ratio (HR) 2.11, 95% CI 1.18-3.76, p 0.01), neutropenia at end of treatment (HR 2.70, 95% CI 1.57-4.65, p <0.001), and receipt of deoxycholate amphotericin B (HR 1.83, 95% CI 1.06-3.16, p 0.03). Treatment practices have changed over the last decade, with an increased use of voriconazole and combination therapies. There has been a 21% increase in survival rate in the last decade.

Invasive fungal diseases in haematopoietic cell transplant recipients and in patients with acute myeloid leukaemia or myelodysplasia in Brazil.

Invasive fungal disease (IFD) shows distinct regional incidence patterns and epidemiological features depending on the geographic region. We conducted a prospective survey in eight centres in Brazil from May 2007 to July 2009. All haematopoietic cell transplant (HCT) recipients and patients with acute myeloid leukaemia (AML) or myelodysplasia (MDS) were followed from admission until 1 year (HCT) or end of consolidation therapy (AML/MDS). The 12-month cumulative incidence (CI) of proven or probable IFD was calculated, and curves were compared using the Grey test. Among 237 AML/MDS patients and 700 HCT recipients (378 allogeneic, 322 autologous), the 1-year CI of IFD in AML/MDS, allogeneic HCT and autologous HCT was 18.7%, 11.3% and 1.9% (p <0.001), respectively. Fusariosis (23 episodes), aspergillosis (20 episodes) and candidiasis (11 episodes) were the most frequent IFD. The 1-year CI of aspergillosis and fusariosis in AML/MDS, allogeneic HCT and autologous HCT were 13.4%, 2.3% and 0% (p <0.001), and 5.2%, 3.8% and 0.6% (p 0.01), respectively. The 6-week probability of survival was 53%, and was lower in cases of fusariosis (41%). We observed a high burden of IFD and a high incidence and mortality for fusariosis in this first multicentre epidemiological study of IFD in haematological patients in Brazil.

Guideline for the management of fever and neutropenia in children with cancer and/or undergoing hematopoietic stem-cell transplantation

To develop an evidence-based guideline for the empiric management of pediatric fever and neutropenia (FN). The International Pediatric Fever and Neutropenia Guideline Panel is a multidisciplinary and multinational group composed of experts in pediatric oncology and infectious disease as well as a patient advocate. The Panel was convened for the purpose of creating this guideline. We followed previously validated procedures for creating evidence-based guidelines. Working groups focused on initial presentation, ongoing management, and empiric antifungal therapy. Each working group developed key clinical questions, conducted systematic reviews of the published literature, and compiled evidence summaries. The Grades of Recommendation Assessment, Development, and Evaluation approach was used to generate summaries, and evidence was classified as high, moderate, low, or very low based on methodologic considerations. Recommendations were made related to initial presentation (risk stratification, initial evaluation, and treatment), ongoing management (modification and cessation of empiric antibiotics), and empiric antifungal treatment (risk stratification, evaluation, and treatment) of pediatric FN. For each recommendation, the strength of the recommendation and level of evidence are presented. This guideline represents an evidence-based approach to FN specific to children with cancer. Although some recommendations are similar to adult-based guidelines, there are key distinctions in multiple areas. Implementation will require adaptation to the local context.